ENCePP Guide on Methodological Standards in Pharmacoepidemiology

5.6.3. Randomised database studies

Randomised database studies can
be considered a special form of an LST where patients included in the trial are
enrolled in a healthcare system with electronic records. Eligible patients may
be identified and flagged automatically by the software, with the advantage of
allowing comparison of included and non-included patients. Database screening or
record linkage can be used to detect and measure outcomes of interest otherwise
assessed through the normal process of care. Patient recruitment, informed
consent and proper documentation of patient information are hurdles that still
need to be addressed in accordance with the applicable legislation for RCTs.
Randomised database studies attempt to combine the advantages of randomisation
and observational database studies. These and other aspects of randomised
database studies are discussed in The
opportunities and challenges of pragmatic point-of-care randomised trials using
routinely collected electronic records: evaluations of two exemplar trials (Health Technol Assess. 2014;18(43):1-146) which illustrates the practical
implementation of randomised studies in general practice databases.

There are few published examples
of randomised database studies, but this design could become more common in the
near future with the increasing computerisation of medical records. Pragmatic randomised
trials using routine electronic health records: putting them to the test (BMJ 2012;344:e55) describes a project to implement randomised trials in the
everyday clinical work of general practitioners, comparing treatments that are
already in common use, and using routinely collected electronic healthcare
records both to identify participants and to gather results.

A particular form of randomised
databases studies is the registry-based randomised trial, which uses an existing
registry as platform for the identification of cases, randomisation and
follow-up. The editorial Randomized Registry Trial — The Next Disruptive Technology in
Clinical Research? (N N Engl J
Med 2013; 369:1579-1581 ) introduces the concept. This hybrid design tries to
achieve both internal and external validity by using a robust design (RCT) in a
data source with higher generalisability (registries). Other examples are the
TASTE trial that followed patients long-term using data from a Scandinavian
registry (Thrombus aspiration during ST-segment elevation myocardial
infarction. N. Engl J Med. 2013;369(17):1587-97) and A registry-based
randomized trial comparing radial and femoral approaches in women undergoing
percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site
for Enhancement of PCI for Women) trial (JACC Cardiovasc Interv. 2014 Aug). A
potential limitation of randomised registry trials is the routine collection of
data on outcomes needed for the trial, such as information on surrogate markers
and adverse events.